Reaction #91064

Reaction equation

cyclopentylmagnesium chloride

methyl 4-chloro-3-(trifluoromethyl)benzoate

→

title compound

Yield 95.8%

Methyl 4-Cyclopentyl-3-(trifluoromethyl)benzoate

Yield 95.8%

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureunder reflux for 2 h
3. 3
   Temperatureto cool to room temperature
4. 4
   Otherquenched with saturated aqueous sodium bicarbonate solution
5. 5
   Filtrationfiltered
6. 6
   ExtractionThe filtrate was extracted with ethyl acetate
7. 7
   DryingThe organic layer was dried over anhydrous sodium sulfate
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   Otherpurified by silica gel column chromatography

Procedure

To zinc(II) chloride (0.5 M solution in tetrahydrofuran, 88.0 mL, 44.0 mmol) was added cyclopentylmagnesium chloride (2 M solution in ether, 20.5 mL, 41.1 mmol). The resulting suspension was stirred at room temperature for 1 h. To the above suspension was added methyl 4-chloro-3-(trifluoromethyl)benzoate (7.00 g, 29.3 mmol) and bis(tri-tert-butylphosphine)palladium (1.35 g, 2.64 mmol) at room temperature. The mixture was heated under reflux for 2 h. The mixture was allowed to cool to room temperature, quenched with saturated aqueous sodium bicarbonate solution and filtered. The filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to give the title compound as an oil (7.64 g). LCMS m/z=273.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.57-1.66 (m, 2H), 1.68-1.82 (m, 2H), 1.82-1.94 (m, 2H), 2.04-221 (m, 2H), 3.33-3.49 (m, 1H), 3.93 (s, 3H), 7.54 (d, J=8.21 Hz, 1H), 8.13 (dd, J=8.34, 1.77 Hz, H), 8.27 (s, 1H).

Source